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LymphomaPhase 1/2NCT00517530

A Dose-Escalating Study of Obinutuzumab in Patients With B-lymphocyte Antigen (CD20+) Malignant Disease (GAUGUIN)

A Phase 1/2 study testing Obinutuzumab in people with Lymphoma, run by Hoffmann-La Roche at 16 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective for the phase I part of the study is to investigate the safety and tolerability of escalating intravenous (IV) doses of obinutuzumab given as monotherapy in participants with CD20+ (tumor-infiltrating lymphocytic) Malignant Disease, including B-cell chronic lymphocytic leukemia (CLL) and… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma
What is being tested?
Obinutuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
134 participants
Where
16 sitesin 2 countries
Study dates
Sep 2007to Nov 2013
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patients, >=18 years of age;
  • Phase 1 only: CD20+ malignant disease (B-cell lymphoma or B-CLL);
  • Phase 2 only: relapsed or refractory indolent NHL, relapsed or refractory aggressive NHL or relapsed or refractory B-CLL
  • Have a clinical indication for treatment as determined by the investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Life expectancy >12 weeks

Who cannot join

  • Prior use of any investigational antibody therapy or other agent within 6 months of study start;
  • Prior use of any anti-cancer vaccine;
  • Prior use of standard anti-lymphoma/leukemia therapy or radiation therapy within 4 weeks of enrollment;
  • Prior use of MabThera (rituximab) within 8 weeks of study entry;
  • Prior administration of radioimmunotherapy 3 months prior to study entry;
  • Central nervous system (CNS) lymphoma.

Trial locations and contacts

16 sites in 2 countries.

16 sites in 2 countries

France15 sites

  • Study site

    Créteil, 94010

  • Study site

    Le Mans, 72015

  • Study site

    Lille, 59037

  • Study site

    Marseille, 13273

  • Study site

    Montpellier, 34295

  • Study site

    Nantes, 44093

  • Study site

    Paris, 75475

  • Study site

    Paris, 75651

  • Study site

    Pessac, 33604

  • Study site

    Pierre-Bénite, 69495

  • Study site

    Rennes, 35033

  • Study site

    Rouen, 76038

  • Study site

    Toulouse, 31059

  • Study site

    Tours, 37044

  • Study site

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Germany1 site

  • Study site

    Cologne, 50924

Other trials in Germany

About this study

Official title: An Open-label, Multicentre, Nonrandomized, Dose-escalating Phase I/II Study, With a Randomized Phase II Part, to Investigate the Safety and Tolerability of RO5072759 Given as Monotherapy in Patients With CD20+ Malignant Disease.

The primary objective for the phase I part of the study is to investigate the safety and tolerability of escalating intravenous (IV) doses of obinutuzumab given as monotherapy in participants with CD20+ (tumor-infiltrating lymphocytic) Malignant Disease, including B-cell chronic lymphocytic leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL). The primary objective for the phase II part of the study is to investigate the efficacy and safety of one dose of obinutuzumab in participants with relapsed/refractory CLL and NHL that is, in turn, either indolent (iNHL) or aggressive (aNHL).

It is an open label dose escalating study in phase I and open label in phase II, but the two doses in iNHL \& aNHL are randomized (to high or low dose of the same open label treatment). CLL was not randomized as only one dose level was used.

Participants with a response who might gain additional benefit from being treated again in the opinion of the investigator may be enrolled in a Retreatment Period.

Conditions
Lymphoma
Being tested
Obinutuzumab
Medical subject headings
Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ObinutuzumabDrug

    Also called RO5072759, GA101

    Obinutuzumab was provided in single-dose glass vials as a freeze-dried powder.

Study groups in NCT00517530
Study groupRoleWhat they receive
Phase I, NHLExperimentalParticipants in this NHL arm received multiple ascending doses between 50 and 2000 mg via intravenous infusion of obinutuzumab.
Receives: Drug: Obinutuzumab
Phase I, CLLExperimentalParticipants in this CLL arm received multiple ascending doses between 400 and 2000 mg via intravenous infusion of obinutuzumab.
Receives: Drug: Obinutuzumab
400/400 mg - Phase II, iNHLExperimentalParticipants in this iNHL arm received an intravenous infusion of obinutuzumab 400 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 400 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
Receives: Drug: Obinutuzumab
1600/800 mg - Phase II, iNHLExperimentalParticipants in this iNHL arm received an intravenous infusion of obinutuzumab 1600 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 800 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
Receives: Drug: Obinutuzumab
400/400 mg - Phase II, aNHLExperimentalParticipants in this aNHL arm received an intravenous infusion of obinutuzumab 400 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 400 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
Receives: Drug: Obinutuzumab
1600/800 mg - Phase II, aNHLExperimentalParticipants in this aNHL arm received an intravenous infusion of obinutuzumab 1600 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 800 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.
Receives: Drug: Obinutuzumab
1000/1000 mg - Phase II, CLLExperimentalParticipants in this CLL arm received an intravenous infusion of obinutuzumab 1000 mg on Days 1, 8, and 15 of Cycle 1 and obinutuzumab 1000 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 10 infusions. Each cycle was 21 days.
Receives: Drug: Obinutuzumab
Retreated ParticipantsExperimentalParticipants who might benefit from retreatment who were allowed to be treated again via intravenous infusion of obinutuzumab at the request of the investigator.
Receives: Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Experienced a Dose-limiting Toxicity in Phase I of the Study

    Dose-limiting toxicities were defined as obinutuzumab-related adverse events occurring within the first 28 days of each administration of obinutuzumab, with the exception of B-cell depletion and lymphopenia which are expected outcomes of treatment with obinutuzumab.

    Measured: Baseline to 28 days after the last infusion of obinutuzumab (up to 6 months)

  2. Percentage of Participants With Best Overall Response in Phase II of the Study

    Best overall response (BOR) was defined as the percentage of participants with a complete response (CR) or partial response (PR)

    Measured: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)

Secondary outcomes (9)

  1. Percentage of Participants With Complete Response (CR/CRu/CRi) in Phase II of the Study

    A complete response was defined as the disappearance of all evidence of disease (NHL) and symptoms; normalization of biochemical abnormalities (NHL); regression of lymph nodes and nodal masses to normal size; decrease of nodes in the sum of the products of the greatest diameters (SPD); regression in size of the spleen and/or liver, should not be palpable, and disappearance of nodules related to lymphoma (CLL). Complete/unconfirmed (CRu) response includes NHL patients with one or more of the following: 1) a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the SPD; 2) Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). Complete Response with Incomplete Bone Marrow Recovery (CRi) was measured only in patients with CLL.

    Measured: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)

  2. Percentage of Participants With Partial Response (PR) in Phase II of the Study

    A PR was defined as a >=50% decrease in SPD of the 6 largest nodes or nodal masses; no increase in size of other nodes, liver, or spleen; regression of splenic and hepatic nodules by >=50% in their SPD or, for single nodules, in the long axis (CLL only); and no new disease sites.

    Measured: by Cutoff Date: 31 March 2012 (within 3 years, 4 months)

  3. Progression-free Survival (PFS) in Phase II of the Study

    PFS was defined as the time from start of treatment to disease progression (PD) or death due to any cause, whichever occurred first. For non-Hodgkin's lymphoma participants, PD was defined as >= 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for participants with a partial response or non-responders or the appearance of any new lesion during or at the end of therapy. For chronic lymphocytic leukemia participants, PD was defined as: (1) A >= 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules); a lymph node with a short axis of < 1.0 cm must increase by >= 50% and to a size of 1.5×1.5 cm or > 1.5 cm in the longest axis. (2) Appearance of any new lesion > 1 cm in the short axis. (4) A new site that is positron emission tomography (PET)-positive with histological confirmation.

    Measured: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)

  4. Duration of Response by Disease Type in Phase II of the Study

    Duration of complete response was defined as the time from the first complete or partial response until disease progression (PD) or death, whichever occurred first. For non-Hodgkin's lymphoma participants, PD was defined as >= 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for participants with a partial response or non-responders or the appearance of any new lesion during or at the end of therapy. For chronic lymphocytic leukemia participants, PD was defined as: (1) A >= 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules); a lymph node with a short axis of < 1.0 cm must increase by >= 50% and to a size of 1.5×1.5 cm or > 1.5 cm in the longest axis. (2) Appearance of any new lesion > 1 cm in the short axis. (4) A new site that is PET-positive with histological confirmation.

    Measured: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)

  5. Participants With Event-Free Survival (EFS) in Phase II of the Study

    EFS is defined as the time from start of treatment to disease progression/relapse, death or, in case of early withdrawal from the treatment period, the (end) date of last dose, whatever comes first.

    Measured: by the end of the follow-up period in Phase II of the study (within 3 years, 4 months)

  6. Pharmacodynamics: Participants With Peripheral B-cell Recovery After Having Had Depletion at End of Treatment During Phase II of the Study

    B-cell depletion was defined in two ways: definition 1 - decrease below 5% baseline level and definition 2 - decrease below 0.04 x 109/L. B-cell recovery was defined in two ways: definition 1 - return to at least 50% of baseline level and definition 2 - return to at least 0.08 x 109/L.

    Measured: by the end of Phase II (within 3 years, 4 months)

  7. Percentage of Retreated Participants With Response

    Patients who might benefit from retreatment were allowed to be treated again at the request of the investigator.

    Measured: by Cutoff Date: 25 November 2013 (within 4 years, 2 months)

  8. Maximum Plasma Concentration (Cmax) of Obinutuzumab in NHL Participants

    Obinutuzumab serum pharmacokinetic (PK) parameters in NHL participants following ascending doses.

    Measured: at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 8 (over 168 days)

  9. Area Under the Concentration-time Curve of Obinutuzumab Administered on Day 1 of Cycle 1 in Phase I of the Study

    Blood samples were taken on Day 1 (pre-infusion, end of infusion, 3-6 hours post-infusion) of Cycle 1. Nonlinear mixed-effects modeling (with NONMEM software) was used to analyze the pooled samples for dose-concentration-time data of obinutuzumab.

    Measured: Day 1 of Cycle 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Aug 2007 (estimated)
  2. Study startSep 2007
  3. Primary completionNov 2013
  4. Study completionNov 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00517530
Sponsor's protocol ID
BO20999
Other IDs
2007-001103-37
Status last verified
Aug 2016
First submitted
16 Aug 2007
Last updated
11 Oct 2016
Data monitoring committee
No

Publications

  • Gibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.

    PubMed 31050355

  • Cartron G, Hourcade-Potelleret F, Morschhauser F, Salles G, Wenger M, Truppel-Hartmann A, Carlile DJ. Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma. Haematologica. 2016 Feb;101(2):226-34. doi: 10.3324/haematol.2015.133421. Epub 2015 Dec 11.

    PubMed 26659915

  • Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. doi: 10.1182/blood-2014-07-586610. Epub 2014 Aug 20.

    PubMed 25143487

  • Morschhauser FA, Cartron G, Thieblemont C, Solal-Celigny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. doi: 10.1200/JCO.2012.46.9585. Epub 2013 Jul 8.

    PubMed 23835718

  • Salles GA, Morschhauser F, Solal-Celigny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. doi: 10.1200/JCO.2012.46.9718. Epub 2013 Jul 8.

    PubMed 23835715

  • Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. doi: 10.1182/blood-2012-01-404368. Epub 2012 Mar 19.

    PubMed 22431570

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Obinutuzumab in people with Lymphoma, run by Hoffmann-La Roche at 16 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Experienced a Dose-limiting Toxicity in Phase I of the Study (time frame: Baseline to 28 days after the last infusion of obinutuzumab (up to 6 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00517530, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2016; AzTrials last refreshed its copy on 6 Nov 2026.

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